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Biomedical subjects

C Ross

Publications and source records attributed to C Ross.

At least 37 records · Page 2Linked to original sources
PubMed2000

Neutralizing antibodies to interferon (IFN) alpha-2a and IFN beta-1a or IFN beta-1b in MS are not cross-reactive.

Sera from patients with MS treated with recombinant interferon (rIFN) alpha-2a, rIFNbeta-1a, or rIFNbeta-1b were analyzed for cross-reacting neutralizing antibodies (NAB). Because cross-reactivity was not found, switching treatment from rIFNbeta-1a or rIFNbeta-1b to rIFNalpha-2a might provide a secondary treatment response in patients with NAB to rIFNbeta-1a or rIFNbeta-1b. A positive treatment response also might be achieved by switching NAB rIFNalpha-2a-positive patients to rIFNbeta-1a or rIFNbeta-1b.

Adult↗
PubMed2000

Treatment of separation anxiety in dogs with clomipramine: results from a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial.

The efficacy and tolerability of clomipramine in the treatment of separation anxiety in dogs was tested in a prospective, randomized, double-blind, placebo-controlled, parallel-group, international multicenter clinical trial. For a diagnosis of separation anxiety, dogs had to exhibit at least one of the following signs in the absence of their owner: destruction, defecation, urination and/or vocalization, as well as the behaviour suggestive of "hyper-attachment" to their owner. A total of 95 dogs were randomized to receive one of the three treatments for 2-3 months: "standard-dose" clomipramine (1 to <2 mg/kg, PO, q. 12 h); "low-dose" clomipramine (0.5 to <1 mg/kg, PO, q. 12 h); and placebo (PO, q. 12 h). All dogs received behavioural therapy. Dogs were examined at four time points (days 0, 28, 56 and 84) after the initiation of therapy. Improvement in each dog's behaviour at days 28, 56 and 84 was evaluated in comparison to its behaviour at day 0.The results showed that, compared to placebo, dogs receiving standard-dose clomipramine were rated improved at least three times faster for the signs destruction, defecation and urination. At most time points, more dogs in the standard-dose clomipramine group were rated improved for the signs destruction, defecation and urination, and in an owner's global assessment of the dog's overall behaviour (p<0.05 at certain time points). However, there were no statistically significant differences at any time point between the standard dose and the placebo groups in the sign vocalization. The low-dose clomipramine group produced no statistically significant effect when compared with placebo. Mild and transient vomiting was noted as a side effect of clomipramine in a small number of dogs.It is concluded that addition of standard-dose (1 to <2 mg/kg, PO, q. 12 h) clomipramine to conventional behavioural therapy for 2-3 months ameliorated the signs of separation anxiety in dogs.

Journal Article↗
PubMed2000

Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2.

PTEN is a tumor suppressor gene mutated in human cancers. Although many mutations target the phosphatase domain, others create a truncated protein lacking the C-terminal PDZ-binding motif or a protein that extends beyond the PDZ-binding motif. Using the yeast two-hybrid system, we isolated a membrane-associated guanylate kinase family protein with multiple PDZ domains [AIP-1 (atrophin interacting protein 1), renamed MAGI-2 (membrane associated guanylate kinase inverted-2)]. MAGI-2 contains eight potential protein-protein interaction domains and is localized to tight junctions in the membrane of epithelial cells. PTEN binds to MAGI-2 through an interaction between the PDZ-binding motif of PTEN and the second PDZ domain of MAGI-2. MAGI-2 enhances the ability of PTEN to suppress Akt activation. Furthermore, certain PTEN mutants have reduced stability, which is restored by adding the minimal PDZ-binding motif back to the truncated protein. We propose that MAGI-2 improves the efficiency of PTEN signaling through assembly of a multiprotein complex at the cell membrane.

Gene Expression Regulation↗
PubMed2000

Clinical benefits of oral irrigation for periodontitis are related to reduction of pro-inflammatory cytokine levels and plaque.

BACKGROUND: Although a growing body of evidence indicates that oral irrigation with water has therapeutic benefits in periodontitis, the mechanisms of action have not been elucidated. The aims of this study were: (1) to analyze the effects of oral irrigation (Water Pik Oral Irrigator) on the clinical signs of adult periodontitis (AP) and on the levels of interleukin-1 beta (IL-beta), prostaglandin-E2 (PGE2), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) in GCF, and (2) to analyze the influence of the periodontitis-related IL-1 genotype (IL-1GT) on these variables. METHOD: A single-center, blinded study in otherwise healthy humans (n= 52) with localized mild to moderate AP was carried out, using the following groups: group A (n= 12), no oral hygiene for 14 days; group B (n=20), routine oral hygiene (ROH) for 14 days; group C (n=20), supra-gingival oral irrigation plus ROH for 14 days. Group A patients were crossed-over to group C for 14 days (=day 28) after a professional prophylaxis. Group assignment was randomized by a coin toss, with the exception of group A subjects, who were self-selected as per recommendations of the internal review board for human subjects. GCF was sampled from 3 study teeth per patient and analyzed for IL-1 beta, PGE2, IL-10 and IFN gamma by ELISA on days 0, 7, 14 and 28. Probing pocket depths (PPD), clinical attachment levels (CAL), bleeding on probing (BOP), gingival index (GI) and plaque index (PI) were measured by a calibrated examiner (TWS) on days 0, 14 and 28. Analysis of covariance was performed using SAS 6.12 and Proc Mixed with group and IL-1GT as the factors and the baseline levels as the covariate, with output being least squares means and least significant difference (LSD). Significant differences were declared if the p-value for the F-statistic was < or =0.05. RESULTS: Oral irrigation plus ROH resulted in a significant reduction in PPD, BOP, GI and PI, as well as IL-beta levels by 7 days and PGE2 levels by 14 days, relative to ROH or no oral hygiene. Interestingly, decreased IL-1 beta levels in patients using oral irrigation plus ROH was accompanied by a trend for increased levels of the "anti-inflammatory" cytokine IL-10. ROH reduced GI, BOP and PI, and PGE2 levels by 14 days, but had no effect on IL-1 beta or IL-10 levels relative to no oral hygiene. The effects of no oral hygiene were reversed by a prophy followed by oral irrigation plus ROH for 14 days. No clinical differences were evident between IL-1 GT (+) patients (n= 1) and GT (-) patients (n=40), but the former had significantly elevated levels of GCF IL-10 and borderline increases in IL-1 beta (p=0.07). CONCLUSIONS: Oral irrigation with water for 14 days had an improved therapeutic benefit for AP over that of routine oral hygiene alone and this improvement was accompanied by a down-modulation of the pro-inflammatory cytokine profile in GCF.

Adult↗
PubMed2000

Detection of autoantibodies to cytokines.

Autoantibodies to various cytokines have been reported in normal individuals and in patients with various infectious and immunoinflammatory disorders, and similar antibodies (Ab) may be induced in patients receiving human recombinant cytokines. The clinical relevance of these Ab is often difficult to evaluate. Not only are in vitro neutralizing cytokine Ab not necessarily neutralizing in vivo, but assays for binding and neutralizing Ab to cytokines are often difficult to interpret. For example, denaturation of immobilized cytokines in immunoblotting techniques and immunometric assays may leave Ab to the native forms of the mediators unrecognized. On the other hand, Ab may bind nonspecifically and/or with biologically irrelevant low affinities, leading to erroneous interpretations. This article describes in detail the use of radioimmunoassays that we have optimized and used successfully for the detection of high-affinity (auto) Ab to IL-1 alpha, IL-6, GM-CSF, and IFN alpha.

Autoantibodies↗
PubMed2000

Immunogenicity of interferon-beta in multiple sclerosis patients: influence of preparation, dosage, dose frequency, and route of administration. Danish Multiple Sclerosis Study Group.

A total of 754 consecutive patients with relapsing-remitting multiple sclerosis were investigated for interferon-beta (IFNbeta) antibodies by protein-G affinity chromatography and antiviral neutralization bioassay during 24 months on 6 MIU (22 microg) of subcutaneous IFNbeta-1a once weekly (n = 143) or three times weekly (n = 160), 6 MIU (30 microg) of intramuscular IFNbeta-1a once weekly (n = 140), or 8 MIU every other day of IFNbeta-1b (n = 311). The proportion of binding antibodies was higher in those receiving IFNbeta-1b compared with 6 MIU of IFNbeta-1a three times weekly (97 vs 89% at 12 months), and fewer became positive if 6 MIU of IFNbeta-1a was administered once weekly (58 vs 89%). Fewer patients on intramuscular than subcutaneous IFNbeta-1a became positive (33 vs 58%). The binding and neutralizing capacities were higher in the IFNbeta-1b group than in the IFNbeta-1a groups; these differences, however, were not significant after 12 months. The number of positive patients varied considerably and depended on the amount of IFN added to the bioassay; adding 10 LU/ml or more masked antibody detection. Antibodies induced by either preparation neutralized both IFNbeta species but not IFNalpha. In conclusion, IFNbeta-induced antibodies are frequently found in multiple sclerosis patients, and IFNbeta-1b is more immunogenic than IFNbeta-1a. The immunogenicity of IFNbeta-1a increases with the frequency of administration and if it is given subcutaneously.

Adolescent↗
PubMed2000

Diabetic foot disorders. A clinical practice guideline. For the American College of Foot and Ankle Surgeons and the American College of Foot and Ankle Orthopedics and Medicine.

Foot ulcerations, infections, and Charcot neuropathic osteoarthropathy are three serious foot complications of diabetes mellitus that can too frequently lead to gangrene and lower limb amputation. Consequently, foot disorders are one of the leading causes of hospitalization for persons with diabetes and can account for expenditures in the billions of dollars annually in the U.S. alone. Although not all foot complications can be prevented, dramatic reductions in their frequency have been obtained through the implementation of a multidisciplinary team approach to patient management. Using this concept, the authors present a Clinical Practice Guideline for diabetic foot disorders based on currently available evidence. The underlying pathophysiology and treatment of diabetic foot ulcers, infections, and the diabetic Charcot foot are thoroughly reviewed. Although these guidelines cannot and should not dictate the standard of care for all affected patients, they are intended to provide evidence-based guidance for general patterns of practice. The goal of a major reduction in diabetic limb amputations is certainly possible if these concepts are embraced and incorporated into patient management protocols.

Arthropathy, Neurogenic↗
PubMed2000

Diabetic foot disorders: a clinical practice guideline. American College of Foot and Ankle Surgeons.

Foot ulcerations, infections, and Charcot neuropathic osteoarthropathy are three serious foot complications of diabetes mellitus that can too frequently lead to gangrene and lower limb amputation. Consequently, foot disorders are one of the leading causes of hospitalization for persons with diabetes and can account for expenditures in the billions of dollars annually in the U.S. alone. Although not all foot complications can be prevented, dramatic reductions in their frequency have been obtained through the implementation of a multidisciplinary team approach to patient management. Using this concept, the authors present a Clinical Practice Guideline for diabetic foot disorders based on currently available evidence. The underlying pathophysiology and treatment of diabetic foot ulcers, infections, and the diabetic Charcot foot are thoroughly reviewed. Although these guidelines cannot and should not dictate the standard of care for all affected patients, they are intended to provide evidence-based guidance for general patterns of practice. The goal of a major reduction in diabetic limb amputations is certainly possible if these concepts are embraced and incorporated into patient management protocols.

Amputation, Surgical↗
PubMed1999

Sex differences in energy expenditure in non-human primates.

Female mammals bear the energetic costs of gestation and lactation. Therefore, it is often assumed that the overall energetic costs are greater for females than they are for males. However, the energetic costs to males of intrasex competition may also be considerable, particularly if males maintain a much larger body size than females. Using data from 19 non-human primates, this paper examines the relationship between male and female energetic costs both in the short term (daily energy expenditure) and the long term (the energetic cost of producing a single offspring). It is shown that the major determinant of sex differences in energetic costs is body size dimorphism. In the long term, the energetic costs are often greater for females, but, when male body size exceeds female body size by 60% or more, male energetic costs are greater than those for females. That is, in highly sexually dimorphic species the energetic costs of gestation and lactation for the females are matched by the energetic costs to the males of maintaining a large body size.

Animals↗
PubMed1999

Status epilepticus on the paediatric intensive care unit-the role of EEG monitoring.

A pilot study was undertaken of the feasibility of continuous EEG monitoring of patients admitted to a Paediatric Intensive Care Unit (PICU) for management of status epilepticus or its immediate sequelae. Eight children were studied and seizure activity was recorded in four patients. Additional information influencing management was obtained: the bedside nurse considered decerebrate posturing in one patient to be a seizure: there were no epileptiform EEG changes. Another patient was considered to have seizures (clonic movements of both upper limbs) following cardiac arrest; the EEG showed electrocerebral silence, and thiopentone treatment was discontinued. In another patient, continuing epileptiform activity on EEG gave intensivists the confidence to use higher than usual doses of thiopentone. The problems encountered were delays in monitoring, once for a CT scan and once because of two admissions within hours of each other. We conclude that EEG monitoring on a PICU is feasible and provides clinically useful information.

Child↗
PubMed1999

Porcine epithelial beta-defensin 1 is expressed in the dorsal tongue at antimicrobial concentrations.

Epithelial cells and phagocytes contain antimicrobial polypeptides that participate in innate host defense. A recently cloned porcine beta-defensin, PBD-1, was detected by Northern organ blots exclusively in the tongue epithelium. We generated recombinant PBD-1 peptide by using a baculovirus-insect cell expression system and obtained two forms (PBD-142 and PBD-138), which differed by N-terminal truncation. Only PBD-142 was found in scrapings of the surface of the dorsal tongue or the buccal mucosa. Immunohistochemical staining with antibody to PBD-142 revealed that PBD-1 was highly concentrated in an approximately 0.1-mm-thick layer in the cornified tips of the filiform (but not fungiform) papillae of the dorsal tongue and in the superficial squamous cell layers of the buccal mucosa. By scraping, extraction, and semiquantitative Western blotting, the concentration of PBD-1 in the dorsal tongue surface and the buccal mucosa was estimated at 20 to 100 micrograms/ml. PBD-1 had antibacterial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Candida albicans in 10 mM sodium phosphate buffer (pH 7.4). Added NaCl progressively inhibited the activity of PBD-1 against E. coli and C. albicans. In 10 mM sodium phosphate with 125 mM NaCl, the combinations of sublethal concentrations of PBD-1 and the porcine neutrophil peptide PG-3, PR-39, or PR-26 showed synergistic activity against E. coli or the multidrug-resistant S. typhimurium DT104. At its physiologic concentration, PBD-1 has antimicrobial effects under both low- and high-salt conditions encountered in the oral cavity and may contribute to the antimicrobial barrier properties of the dorsal tongue and oral epithelium.

Amino Acid Sequence↗
PubMed1998

Endothelial NADPH oxidase as the source of oxidants in lungs exposed to ischemia or high K+.

We have previously demonstrated the generation of reactive oxygen species (ROS) in cultured bovine pulmonary artery endothelial cells (BPAECs) and in isolated perfused rat lungs exposed to high K+ and during global lung ischemia. The present study evaluates the NADPH oxidase pathway as a source of ROS in these models. ROS production, detected by oxidation of the fluorophore, dichlorodihydrofluorescein, increased 2.5-fold in BPAECs and 6-fold in rat or mouse lungs exposed to high (24 mmol/L) K+. ROS generation was markedly inhibited by diphenyliodonium, a flavoprotein inhibitor, and by the synthetic peptide PR-39, an inhibitor of NADPH oxidase assembly, whereas allopurinol had no effect. With ischemia (1 hour), ROS generation by rat and mouse lungs increased 7-fold; PR-39 showed concentration-dependent inhibition of ROS production, with 50% inhibition at 3 micromol/L PR-39. ROS production in lungs exposed to high K+ or ischemia was essentially abolished in mice with a "knockout" of gp91(phox), a membrane-localized cytochrome component of NADPH oxidase; increased ROS production by these lungs after anoxia/reoxygenation was similar to control. PR-39 also inhibited ischemia and the high K+-mediated increase in lung thiobarbituric acid reactive substance. Western blotting of BPAECs and immunocytochemistry of BPAECs and rat and mouse lungs showed the presence of p47phox, a cytoplasmic component of NADPH oxidase and the putative target for PR-39 inhibition. In situ fluorescence imaging in the intact lung demonstrated that the increased dichlorofluorescein fluorescence in these models of ROS generation was localized primarily to the pulmonary endothelium. These studies demonstrate that ROS production in lungs exposed to ischemia or high K+ results from assembly and activation of a membrane-associated NAPDH oxidase of the pulmonary endothelium.

Animals↗
PubMed1998

Antibody to granulocyte-macrophage colony-stimulating factor is a dominant anti-cytokine activity in human IgG preparations.

Pharmaceutical preparations of normal human immunoglobulin (IgG) are known to contain high-avidity and neutralizing antibodies (Ab) to the cytokines interleukin (IL)-1alpha, IL-6, and interferon (IFN)alpha. To test for other cytokine Ab, 23 batches of IgG were tested for saturable binding to eight 125I-labeled recombinant cytokines. All batches bound granulocyte-macrophage colony-stimulating factor (GM-CSF) with high avidity (Kav approximately 10 pmol/L) and capacities of up to 5 mumol GM-CSF/mol IgG. Only 1 of 15 batches bound IL-5, also with high avidity, whereas 13 of 15 batches bound to IL-10 but with lower capacities and avidities. None of the IgG preparations bound IL-1 receptor antagonist (IL-1ra), IL-2, IL-3, IL-4, or G-CSF. Cross-binding and absorption analyses revealed identical or slightly stronger binding of recombinant GM-CSF, IL-5, and IL-10 than their native counterparts. GM-CSF-IgG complexes did not bind to cellular GM-CSF receptors, but Fc-dependent binding occurred to blood polymorphonuclear cells. Increased binding of GM-CSF to patient sera correlated positively with the binding capacities of infused IgG preparations. Patient and normal sera did not interfere with the binding of Ab to GM-CSF. From these and previous experiments, we conclude that pools of normal human IgG contain variable amounts of specific and high-avidity Ab to some cytokines, and that Ab to GM-CSF constitute a dominant anti-cytokine activity in these preparations. These Ab are available for reaction in vivo following IgG therapy.

Adult↗
PubMed1998

Phylogenetic analysis of anthropoid relationships.

The relationships of anthropoids to other primates are currently debated, as are the relationships among early fossil anthropoids and crown anthropoids. To resolve these issues, data on 291 morphological characters were collected for 57 taxa of living and fossil primates and analyzed using PAUP and MacClade. The dental evidence provides weak support for the notion of an adapid origin for anthropoids, the cranial evidence supports the tarsier-anthropoid hypothesis, and the postcranial evidence supports a monophyletic Prosimii and a monophyletic Anthropoidea. Combining these data into a single data set produces almost universal support for a tarsier-anthropoid clade nested within omomyids. Eosimias and Afrotarsius are certainly members of this clade, and probably basal anthropoids, although the Shanghuang petrosal may not belong to Eosimias. The tree derived from the combined data set resembles the tree derived from the cranial data set rather than the larger dental data set. This may be attributable to relatively slower evolution in the cranial characters. The combined data set shows Anthropoidea to be monophyletic but the features traditionally held to be anthropoid synapomorphies are found to have evolved mosaically. Parapithecines are the sister taxon to crown anthropoids; qatraniines and oligopithecids are more distantly related sister taxa. There is support for a relationship of a Tarsius + Anthropoidea clade with either washakiines on Uintanius. These elements of tree topology remain fairly stable under different assumptions sets, but overall, tree topology is not robust. Previously divergent hypotheses regarding anthropoid relationships are attributable to the use of restricted data sets. This large data set enables the adapid-anthropoid hypothesis to be rejected, and unites Tarsius, Anthropoidea and Omomyiformes within a clade, Haplorhini. However, relationships among these three taxa cannot be convincingly resolved at present.

Animals↗